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Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

  • Wang, Bing (Department of Clinical Lab., the 81th Hospital of PLA) ;
  • He, Yu-Jie (Department of Clinical Lab., the 81th Hospital of PLA) ;
  • Tian, Ying-Xing (Department of Clinical Lab., the 81th Hospital of PLA) ;
  • Yang, Rui-Ning (Department of Clinical Lab., the 81th Hospital of PLA) ;
  • Zhu, Yue-Rong (Department of Clinical Lab., the 81th Hospital of PLA) ;
  • Qiu, Hong (Department of Clinical Lab., the 81th Hospital of PLA)
  • Published : 2014.12.18

Abstract

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Results: Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case, the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve ($AUC^{ROC}$) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665). Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.

Keywords

References

  1. Asleh R, Ward J, Levy NS, et al (2014). Haptoglobin genotypedependent differences in macrophage lysosomal oxidative injury. J Biol Chem, 23, 16313-25.
  2. Bertaggia E, Scabia G, Dalise S, et al (2014). Haptoglobin is required to prevent oxidative stress and muscle atrophy. PLoS One, 9, 0100745. https://doi.org/10.1371/journal.pone.0100745
  3. Chih-Ho Lai, Nai-Wen Chang, Chin-Fen Lin, et al (2010). Proteomics-based identification of haptoglobin as a novel plasma biomarker in oral squamous cell carcinoma. Clinica Chimica Acta, 411, 984-91. https://doi.org/10.1016/j.cca.2010.03.028
  4. Ding Y, Xuan W, Chen C, et al (2014). Differences in carcinoembryonic antigen levels between colon and rectal cancer. Mol Clin Oncol, 2, 618-22.
  5. Farooqui MS, Mittal A, Poudel B, et al (2012). Improved diagnostic accuracy of pancreatic diseases with a combination of various novel serum biomarkers. Asian Pac J Cancer Prev, 13, 2171-74. https://doi.org/10.7314/APJCP.2012.13.5.2171
  6. Fujita K, Shimomura M, Uemura M, et al (2014). Serum fucosylated haptoglobin as a novel prognostic biomarker predicting high-Gleason prostate cancer. Prostate, 74, 1052-58. https://doi.org/10.1002/pros.22824
  7. Jessie K, Jayapalan JJ, Ong KC, et al (2013). Aberrant proteins in the saliva of patients with oral squamous cell carcinoma. Electrophoresis, 34, 2495-502. https://doi.org/10.1002/elps.201300107
  8. Juan HF, Chen JH, Hsu WT, et al (2004). Identification of tumorassociated plasma biomarkers using proteomic techniques; from mouse to human. Proteomics, 4, 2766-75. https://doi.org/10.1002/pmic.200400785
  9. Kang SM, Sung HJ, Ahn JM, et al (2011). The Haptoglobin beta chain as a supportive biomarker for human lung cancers. Mol Biosyst, 7, 1167-75. https://doi.org/10.1039/c0mb00242a
  10. Langlois MR, Delanghe (1996). Biological and clinical significance of haptoglobin polymorphism in hunmans. Clin Chem, 42, 1589-600.
  11. Lee KJ, Yi SW, Chung MJ, et al (2013). Serum CA 19-9 and CEA levels as a prognostic factor in pancreatic adenocarcinoma. Yonsei Med J, 54, 643-9. https://doi.org/10.3349/ymj.2013.54.3.643
  12. Melamed-Frank M, Lache O, Enav B I, et al (2001). Structurefunction analysis of the antioxidant properties of haptoglobin. Blood, 98, 3693-8. https://doi.org/10.1182/blood.V98.13.3693
  13. Schneider J, Bitterlich N, Velcovsky H G, et al (2005). Fuzzy logicbased tumor-marker profiles improved sensitivity in the diagnosis of lung cancer. Proteomics, 5, 4581-8. https://doi.org/10.1002/pmic.200401309
  14. Tan W, Wang F, Guo D, et al (2014). High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent-onset rheumatoid arthritis patients. Int J Rheum Dis, 2014, 12380 [Epub ahead of print].
  15. Zhu J, Lin Z, Wu J, et al (2014). Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies. J Proteome Res, 13, 2986-97. https://doi.org/10.1021/pr500128t

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